A partial loss-of-function variant in STAT6 protects against type 2 asthma.

Background: Signal transducer and activator of transcription 6 (STAT6) is central to type 2 (T2) inflammation, and common noncoding variants at the STAT6 locus associate with various T2 inflammatory traits, including diseases, and its pathway is widely targeted in asthma treatment.

Objective: We sought to test the association of a rare missense variant in STAT6, p.L406P, with T2 inflammatory traits, including the risk of asthma and allergic diseases, and to characterize its functional consequences in cell culture.

Variants in the autoimmune disease risk locus influence the regulatory network in immune cells and salivary gland.

Fine mapping and bioinformatic analysis of the genetic risk association in Sjögren's Disease (SjD) and Systemic Lupus Erythematosus (SLE) identified five common SNPs with functional evidence in immune cell types: rs4938573, rs57494551, rs4938572, rs4936443, rs7117261. Functional interrogation of nuclear protein binding affinity, enhancer/promoter regulatory activity, and chromatin-chromatin interactions in immune, salivary gland epithelial, and kidney epithelial cells revealed cell type-specific allelic effects for all five SNPs that expanded regulation beyond effects on and expression. Mapping the local chromatin regulatory network revealed several additional genes of interest, including .

Genetics and epigenetics of primary Sjögren syndrome: implications for future therapies.

In primary Sjögren syndrome (pSS), chronic inflammation of exocrine glands results in tissue destruction and sicca symptoms, primarily of the mouth and eyes. Fatigue, arthralgia and myalgia are also common symptoms, whereas extraglandular manifestations that involve the respiratory, nervous and vascular systems occur in a subset of patients. The disease predominantly affects women, with an estimated female to male ratio of 14 to 1.